Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation
Sébastien Sart1, Liqing Song2, Yan Li2
1Hydrodynamics Laboratory, CNRS UMR 7646, Ecole Polytechnique, 91120 Palaiseau, France.
Abstract:
Reactive oxygen species (ROS) have long been considered as pathological agents inducing apoptosis under adverse culture conditions. However, recent findings have challenged this dogma and physiological levels of ROS are now considered as secondary messengers, mediating numerous cellular functions in stem cells. Stem cells represent important tools for tissue engineering, drug screening, and disease modeling. However, the safe use of stem cells for clinical applications still requires culture improvements to obtain functional cells. With the examples of mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs), this review investigates the roles of ROS in the maintenance of self-renewal, proliferation, and differentiation of stem cells. In addition, this work highlights that the tight control of stem cell microenvironment, including cell organization, and metabolic and mechanical environments, may be an effective approach to regulate endogenous ROS generation. Taken together, this paper indicates the need for better quantification of ROS towards the accurate control of stem cell fate.
Insights
Reactive oxygen species (ROS) are vital messengers in stem cells, not just harmful agents. Controlling ROS via the stem cell microenvironment is key for self-renewal, proliferation, and differentiation in clinical applications.
Area of Science:
- Cell Biology
- Stem Cell Biology
- Biochemistry
Background:
- Reactive oxygen species (ROS) were traditionally viewed as pathological agents causing cell death.
- Emerging evidence indicates physiological ROS levels act as crucial secondary messengers in stem cell functions.
- Stem cells are vital for regenerative medicine, drug discovery, and disease modeling, necessitating optimized culture methods.
Purpose of the Study:
- To review the dual role of ROS in stem cell biology, focusing on self-renewal, proliferation, and differentiation.
- To explore how microenvironmental factors regulate endogenous ROS production in stem cells.
- To emphasize the need for precise ROS quantification for controlled stem cell fate.
Main Methods:
- Literature review focusing on mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs).
- Analysis of studies investigating ROS signaling in stem cell maintenance and function.
- Discussion of microenvironmental influences (organizational, metabolic, mechanical) on ROS generation.
Main Results:
- Physiological ROS levels are essential for mediating stem cell functions, challenging the view of ROS as solely detrimental.
- The stem cell microenvironment, encompassing cell organization and metabolic/mechanical cues, can be modulated to control ROS levels.
- Mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs) exhibit distinct ROS-dependent regulatory mechanisms.
Conclusions:
- ROS play a critical role in maintaining stem cell identity and function, acting as signaling molecules.
- Regulating the stem cell microenvironment offers a promising strategy for controlling endogenous ROS and optimizing stem cell behavior.
- Accurate quantification of ROS is essential for precise control over stem cell fate and successful clinical translation.
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